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EMA recommends immediate recall of the multiple sclerosis medicine Zinbryta (Daclizumab)

The Paul-Ehrlich-Institut (PEI), Federal Institute for Vaccines and Biomedicines has received reports on serious cases of autoimmune reactions in patients with multiple sclerosis treated with the antibody Daclizumab (see note on the PEI website from 2 March 2018). Upon this report, the marketing authorisation holder notified the authorities that it would renounce the marketing authorisation and initiate a recall at its own discretion. The European Medicines Agency (EMA) has now recommended a suspension and a recall of Zinbryta (Daclizumab)

On 1 March 2018, the marketing authorisation holder of Zinbryta, Biogen Idec Ltd., had already reported that it would renounce the marketing authorisation of Zinbryta at its own responsibility and initiate a recall of the medicinal product. The EMA has now recommended the suspension of the marketing authorisation and the immediate recall of the multiple sclerosis medicine Zinbryta (Daclizumab), after twelve reports in total about serious inflammatory disorders of the brain (encephalitis and meningoencephalitis) became known worldwide. Four of the cases were fatal. Most of the cases occurred within eight months after the beginning of the treatment.

The currently available evidence-based data point to a risk of serious brain disorders due to autoimmune related reactions in connection with the treatment of Zinbryta. The data available also reveal a possible causative relationship between Zinbryta and other immune-mediated diseases such as blood count changes, thyreoiditis, or glomerulonephritis.

Information for patients

  • If you are treated with Zinbryta, please contact your doctor to discuss your future treatment options.
  • Refrain from receiving any further Zinbryta injections.
  • Please inform your doctor without delay if you have any symptoms such as persistent high temperature, severe headache, nausea (dizziness), tiredness, yellow discolouration of your skin or your eyeballs, and vomiting. These symptoms could be signs of an adverse reaction to Zinbryta.
  • Your doctor will continue to check your liver values regularly up to six months following the discontinuation of treatment with Zinbryta.
  • If you are participating in a clinical study with Zinbryta, please contact your treating doctor.

Information for healthcare professionals

  • Do not treat any new patients with Zinbryta.
  • Contact your patients who are currently being treated with Zinbrya as soon as possible and discontinue treatment. Consider alternative forms of treatment.
  • Patients who discontinue treatment should be monitored over a period of six months after the last dose of Zinbryta at least on a monthly basis, or, if indicated, more frequently.
  • Please ask your patients to report any symptoms pointing to adverse effects, such as long-term fever, severe headache, tiredness, jaundice, nausea, or vomiting immediately.
  • A recall of Zinbryta from pharmacies and hospitals will be performed in the EU.

A preceding PRAC evaluation in 2017 showed that unforeseeable and potentially lethal immune-mediated liver damage can occur with Zinbryta up to six months after the end of the treatment. PRAC concluded that patients who discontinue treatment should be monitored accordingly.

More about Zinbryta

Zinbryta was authorised in 2016 for the treatment of relapsing forms of multiple sclerosis. After examination of the effects of the product on the liver in 2017, its use was restricted to adult patients with relapsing multiple sclerosis (RMS) who did not sufficiently respond to at least two disease-modifying therapies (DMT) and in whom treatment with any other DMT is contraindicated or unsuitable for any other reasons. More than 8,000 patients worldwide have been treated with Zinbryta. The majority of patients in the EU were treated in Germany.

Mechanism of action

Daclizumab is a humanised IgG1 monoclonal antibody that binds to CD25 (IL-2Rα), and prevents IL-2 binding to CD25. Daclizumab modulates IL-2 signalling by blocking CD25-dependent, high-affinity IL-2 receptor signalling, resulting in higher levels of IL-2 available for signalling through the intermediate-affinity IL-2 receptor. Key effects of this IL-2 pathway modulation potentially related to the therapeutic effects of daclizumab in MS include selective antagonism of activated T-cell responses, and expansion of immunoregulatory CD56bright natural killer (NK) cells, which have been shown to selectively decrease activated T-cells. Together, these immunomodulatory effects of daclizumab are believed to reduce CNS pathology in MS and thereby reduce the occurrence of relapses and disability progression.

The manner in which the mechanism of action of Zinbryta has led to the above-mentioned cases of autoimmune diseases is the subject of ongoing investigations.

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